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Published on: November 27, 2019
Selective A2A adenosine agonist ATL-146e attenuates acute lethal liver injury in mice
Masaru Odashima1, Michiro Otaka, Mario Jin
1Department of Gastroenterology, Akita University School of Medicine, 1-1-1 Hondo, Akita, 010-8543, Japan.
Background:
D-Galactosamine (GalN)/lipopolysaccharide (LPS)-induced liver injury is an experimental model of fulminant hepatic failure in which tumor necrosis factor-alpha (TNF-alpha) plays a pivotal role. We examined the effects of a highly selective adenosine A2A receptor agonist (ATL-146e) on GalN/LPS-induced fulminant hepatic failure.
Methods:
Mice were given an intraperitoneal dose of GalN (800 mg/g body weight)/LPS (100 ng/g body weight) with and without ATL-146e (0.01 microg/kg) treatment. Liver injury was assessed biochemically and histologically. Also, TNF-alpha levels in the serum were determined.
Results:
The serum liver enzyme (ALT) level in vehicle-treated mice was 20 960 +/- 2800 IU/ml and was reduced by 63% to 7800 +/- 1670 IU/ml by treatment with 0.01 microg/kg per minute ATL146e, P < 0.05. Treatment with ATL-146e significantly reduced serum TNF-alpha and greatly reduced inflammation assessed by histopathologic examination compared with control mice treated with GalN/LPS. ATL-146e also reduced lethality at 12 h from 65% to 13%.
Conclusion:
The present findings suggest that the highly selective adenosine A2A receptor agonist (ATL-146e) prevents endotoxin-induced lethal liver injury by suppression of TNF-alpha secretion.
